Avoiding New Biopsies by Identification of IDH1 and TERT Promoter Mutation in Nondiagnostic Biopsies From Glioma Patients

Neurosurgery (87): E513–E519

Biopsies in patients with a suspected glioma are occasionally nondiagnostic.

OBJECTIVE: To explore the utility of molecular testing in this setting by determining whether IDH1 and TERT promoter (pTERT) mutations could be detected in nondiagnostic biopsies from glioma patients. METHODS: Using SNaPshot polymerase chain reaction, we retrospectively assessed IDH1 and pTERT mutation status in nondiagnostic biopsies from 28 glioma patients.

RESULTS: The nondiagnostic biopsy (needle biopsy n = 25, open or endoscopic biopsy n = 3) consisted of slight glial cell hypercellularity, hemorrhage, and/or necrosis. After another biopsy (n = 23) or a subsequent surgical resection (n = 5) the diagnosis was an IDH1-wildtype (WT) pTERT-mutant glioma (glioblastoma n = 16, astrocytoma n = 4), an IDH1-mutant pTERT-mutant oligodendroglioma (n = 1), an IDH1-mutant pTERT-WT astrocytoma (n = 1), and an IDH1-WT pTERT-WT glioblastoma (n = 6). An IDH1 mutation was identified in the nondiagnostic biopsies of the 2 IDH-mutant gliomas, and a pTERT mutation in the nondiagnostic biopsies of 16 out of the 21 of pTERTmutant-gliomas (76%). Overall, an IDH1 and/or a pTERT mutation were detected in 17 out of 28 (61%) of nondiagnostic biopsies. Retrospective analysis of the nondiagnostic biopsies based on these results and on imaging characteristics suggested that a new biopsy could have been avoided in 6 patients in whom a diagnosis of “molecular glioblastoma” could have been done with a high level of confidence.

CONCLUSION: In the present series, IDH1 and pTERT mutations could be detected in a high proportion of nondiagnostic biopsies from glioma patients. Molecular testing may facilitate the interpretation of nondiagnostic biopsies in patients with a suspected glioma.

Development and validation of the Skills Assessment in Microsurgery for Brain Aneurysms (SAMBA) instrument for predicting proficiency in aneurysm surgery

J Neurosurg 133:190–196, 2020

Surgical performance evaluation was first described with the OSATS (Objective Structured Assessment of Technical Skills) and modified for aneurysm microsurgery simulation with the OSAACS (Objective Structured Assessment of Aneurysm Clipping Skills). These methods rely on the subjective opinions of evaluators, however, and there is a lack of objective evaluation for proficiency in the microsurgical treatment of brain aneurysms.

The authors present a new instrument, the Skill Assessment in Microsurgery for Brain Aneurysms (SAMBA) scale, which can be used similarly in a simulation model and in the treatment of unruptured middle cerebral artery (MCA) aneurysms to predict surgical performance; the authors also report on its validation.

METHODS The SAMBA scale was created by consensus among 5 vascular neurosurgeons from 2 different neurosurgical departments. SAMBA results were analyzed using descriptive statistics, Cronbach’s alpha indexes, and multivariate ANOVA analyses (p < 0.05).

RESULTS Expert, intermediate-level, and novice surgeons scored, respectively, an average of 33.9, 27.1, and 16.4 points in the real surgery and 33.3, 27.3, and 19.4 points in the simulation. The SAMBA interrater reliability index was 0.995 for the real surgery and 0.996 for the simulated surgery; the intrarater reliability was 0.983 (Cronbach’s alpha). In both the simulation and the real surgery settings, the average scores achieved by members of each group (expert, intermediate level, and novice) were significantly different (p < 0.001). Scores among novice surgeons were more diverse (coefficient of variation = 12.4).

CONCLUSIONS Predictive validation of the placenta brain aneurysm model has been previously reported, but the SAMBA scale adds an objective scoring system to verify microsurgical ability in this complex operation, stratifying proficiency by points. The SAMBA scale can be used as an interface between learning and practicing, as it can be applied in a safe and controlled environment, such as is provided by a placenta model, with similar results obtained in real surgery, predicting real surgical performance.


Prospects of Photo- and Thermoacoustic Imaging in Neurosurgery

Neurosurgery 87:11–24, 2020

The evolution of neurosurgery has been, and continues to be, closely associated with innovations in technology.

Modern neurosurgery is wed to imaging technology and the future promises even more dependence on anatomic and, perhaps more importantly, functional imaging.

The photoacoustic phenomenon was described nearly 140 yr ago; however, biomedical applications for this technology have only recently received significant attention.

Light-based photoacoustic and microwave-based thermoacoustic technologies represent novel biomedical imaging modalities with broad application potential within and beyond neurosurgery. These technologies offer excellent imaging resolution while generally considered safer,more portable, versatile, and convenient than current imaging technologies. In this review,we summarize the current state of knowledge regarding photoacoustic and thermoacoustic imaging and their potential impact on the field of neurosurgery.

NTMS mapping of non-primary motor areas in brain tumour patients and healthy volunteers

Acta Neurochirurgica (2020) 162:407–416

Navigated transcranial magnetic stimulation (nTMS) has been increasingly used for presurgical cortical mapping of the primary motor cortex (M1) but remains controversial for the evaluation of non-primary motor areas (NPMA). This study investigates clinical and neurophysiological parameters in brain tumour patients and healthy volunteers to decide whether singlepulse biphasic nTMS allows to reliably elicite MEP outside from M1 or not.

Materials and methods Twelve brain tumour patients and six healthy volunteers underwent M1 nTMS mapping. NPMA nTMS mapping followed using 120% and 150% M1 resting motor threshold (RMT) stimulation intensity. Spearman’s correlation analysis tested the association of clinical and neurophysiological parameters between M1 and NPMA mapping.

Results A total of 88.81% of nTMS stimulations in NPMA in patients/83.87% in healthy volunteers in patients/83.87% in healthy volunteers did not result in MEPs ≥ 50 μV. Positive nTMS mapping in NPMA correlated with higher stimulation intensity and larger M1 areas in patients (120% M1 RMT SI p = 0.005/150%M1 RMT SI p = 0.198).

Conclusion Our findings indicate that in case of positive nTMS mapping in NPMA, MEPs originate mostly from M1. For future studies, MEP parameters and TMS coil rotation should be studied closely to assess the risk for postoperative motor deterioration.

Biomechanics of a novel reversibly expandable dynamic craniotomy bone flap fixation plate

J Neurosurg 132:560–567, 2020

Biomechanical evaluation of a novel expandable cranial fixation plate was assessed in cadavers. The dynamic craniotomy procedure uses low-profile reversibly expandable plates that allow cranial decompression by providing for intracranial volume expansion without removal of the bone flap. The plates allow reversible outward movement of the bone flap upon an increase in intracranial pressure (ICP) and also retract the bone flap and prevent it from sinking inside the cranium once the ICP normalizes.

METHODS A comparative evaluation of the extent of ICP control with an increase in intracranial volume between various bone flap fixation techniques was undertaken along with testing of the expandable plate compliance. Static compression tests of the plates were performed to assess bone flap fixation and prevention of sinking. Quasi-static shear tension testing of the plates was undertaken to test the tolerance of the plates for expansion. Fatigue shear tension evaluation of the plates was undertaken to assess tolerance for repetitive expansion and contraction.

RESULTS The dynamic craniotomy provided superior control of ICP with an increase in intracranial volume compared to the hinged craniotomy and standard craniotomy techniques (p < 0.001). Static compression results revealed that the plates withstood bone flap sinkage with a mean peak load of 643.3 ± 26.1 N and a mean inward bone flap displacement of 1.92 ± 0.09 mm. Static shear tension results indicated that the plates could withstand a peak expansion of 71.6 mm. Dynamic shear tension testing of the plates with repetitive 15-mm outward expansion and retraction for a total of up to 500 cycles revealed no cracking and no failure points.

CONCLUSIONS The reversibly expandable plates provide for a low-profile bone flap fixation with rigid restriction of bone flap sinking and also enable cranial decompression with a high tolerance for repetitive expansion and contraction.

The temporoinsular projection system: an anatomical study

J Neurosurg 132:615–623, 2020

Connections between the insular cortex and the amygdaloid complex have been demonstrated using various techniques. Although functionally well connected, the precise anatomical substrate through which the amygdaloid complex and the insula are wired remains unknown. In 1960, Klingler briefly described the “fasciculus amygdaloinsularis,” a white matter tract connecting the posterior insula with the amygdala. The existence of such a fasciculus seems likely but has not been firmly established, and the reported literature does not include a thorough description and documentation of its anatomy. In this fiber dissection study the authors sought to elucidate the pathway connecting the insular cortex and the mesial temporal lobe.

METHODS Fourteen brain specimens obtained at routine autopsy were dissected according to Klingler’s fiber dissection technique. After fixation and freezing, anatomical dissections were performed in a stepwise progressive fashion.

RESULTS The insula is connected with the opercula of the frontal, parietal, and temporal lobes through the extreme capsule, which represents a network of short association fibers. At the limen insulae, white matter fibers from the extreme capsule converge and loop around the uncinate fasciculus toward the temporal pole and the mesial temporal lobe, including the amygdaloid complex.

CONCLUSIONS The insula and the mesial temporal lobe are directly connected through white matter fibers in the extreme capsule, resulting in the appearance of a single amygdaloinsular fasciculus. This apparent fasciculus is part of the broader network of short association fibers of the extreme capsule, which connects the entire insular cortex with the temporal pole and the amygdaloid complex. The authors propose the term “temporoinsular projection system” (TIPS) for this complex.

Key anatomical landmarks for middle fossa surgery: a surgical anatomy study

J Neurosurg 131:1561–1570, 2019

Middle fossa surgery is challenging, and reliable surgical landmarks are essential to perform accurate and safe surgery. Although many descriptions of the middle fossa components have been published, a clinically practical description of this very complex anatomical region is lacking. Small structure arrangements in this area are often not well visualized or accurately demarcated with neuronavigation systems. The objective is to describe a “roadmap” of key surgical reference points and landmarks during middle fossa surgery to help the surgeon predict where critical structures will be located.

METHODS The authors studied 40 dry skulls (80 sides) obtained from the anatomical board at their institution. Measurements of anatomical structures in the middle fossa were made with a digital caliper and a protractor, taking as reference the middle point of the external auditory canal (MEAC). The results were statistically analyzed.

RESULTS The petrous part of the temporal bone was found at a mean of 16 mm anterior and 24 mm posterior to the MEAC. In 87% and 99% of the sides, the foramen ovale and foramen spinosum, respectively, were encountered deep to the zygomatic root. The posterior aspect of the greater superficial petrosal nerve (GSPN) groove was a mean of 6 mm anterior and 25 mm medial to the MEAC, nearly parallel to the petrous ridge. The main axis of the IAC projected to the root of the zygoma in all cases. The internal auditory canal (IAC) porus was found 5.5 mm lateral and 4.5 mm deep to the lateral aspect of the trigeminal impression along the petrous ridge (mean measurement values). A projection from this point to the middle aspect of the root of the zygoma, being posterior to the GSPN groove, could estimate the orientation of the IAC.

CONCLUSIONS In middle fossa approaches, the external acoustic canal is a reliable reference before skin incision, whereas the zygomatic root becomes important after the skin incision. Deep structures can be related to these 2 anatomical structures. An easy method to predict the location of the IAC in surgery is described. Careful study of the preoperative imaging is essential to adapt this knowledge to the individual anatomy of the patient.

Prospective validation of a molecular prognostication panel for clival chordoma

J Neurosurg 130:1528–1537, 2019

There are currently no reliable means to predict the wide variability in behavior of clival chordoma so as to guide clinical decision-making and patient education. Furthermore, there is no method of predicting a tumor’s response to radiation therapy.

METHODS A molecular prognostication panel, consisting of fluorescence in situ hybridization (FISH) of the chromosomal loci 1p36 and 9p21, as well as immunohistochemistry for Ki-67, was prospectively evaluated in 105 clival chordoma samples from November 2007 to April 2016. The results were correlated with overall progression-free survival after surgery (PFSS), as well as progression-free survival after radiotherapy (PFSR).

RESULTS Although Ki-67 and the percentages of tumor cells with 1q25 hyperploidy, 1p36 deletions, and homozygous 9p21 deletions were all found to be predictive of PFSS and PFSR in univariate analyses, only 1p36 deletions and homozygous 9p21 deletions were shown to be independently predictive in a multivariate analysis. Using a prognostication calculator formulated by a separate multivariate Cox model, two 1p36 deletion strata (0%–15% and > 15% deleted tumor cells) and three 9p21 homozygous deletion strata (0%–3%, 4%–24%, and ≥ 25% deleted tumor cells) accounted for a range of cumulative hazard ratios of 1 to 56.1 for PFSS and 1 to 75.6 for PFSR.

CONCLUSIONS Homozygous 9p21 deletions and 1p36 deletions are independent prognostic factors in clival chordoma and can account for a wide spectrum of overall PFSS and PFSR. This panel can be used to guide management after resection of clival chordomas.


Potential of Human Nucleus Pulposus-Like Cells Derived From Umbilical Cord to Treat Degenerative Disc Disease

Neurosurgery 84:272–283, 2019

Degenerative disc disease (DDD) is a common spinal disorder that manifests with neck and lower back pain caused by the degeneration of intervertebral discs (IVDs). Currently, there is no treatment to cure this debilitating ailment.

OBJECTIVE: To investigate the potential of nucleus pulposus (NP)-like cells (NPCs) derived from human umbilical cord mesenchymal stem cells (MSCs) to restore degenerated IVDs using a rabbit DDD model.

METHODS: NPCs differentiated from MSC swere characterized using quantitative real-time reverse transcription polymerase chain reaction and immunocytochemical analysis. MSCs and NPCs were labeled with fluorescent dye, PKH26, and transplanted into degenerated IVDs of a rabbit model of DDD (n = 9 each). Magnetic resonance imaging of the IVDs was performed before and after IVD degeneration, and following cell transplantation. IVDs were extracted 8 wk post-transplantation and analyzed by various biochemical, immunohistological, and molecular techniques.

RESULTS: NPC derivatives of MSCs expressed known NP-specific genes, SOX9, ACAN, COL2, FOXF1, and KRT19. Transplanted cells survived, dispersed, and integrated into the degenerated IVDs. IVDs augmented with NPCs showed significant improvement in the histology, cellularity, sulfated glycosaminoglycan andwater contents of the NP. In addition, expression of human genes, SOX9, ACAN, COL2, FOXF1, KRT19, PAX6, CA12, and COMP, aswell as proteins, SOX9, ACAN, COL2, and FOXF1, suggest NP biosynthesis due to transplantation of NPCs. Based on these results, a molecular mechanism for NP regeneration was proposed.

CONCLUSION: The findings of this study demonstrating feasibility and efficacy of NPCs to regenerate NP should spur interest for clinical studies to treat DDD using cell therapy.

Microsurgical anatomy of the central core of the brain

J Neurosurg 129:752–769, 2018

The purpose of this study was to describe in detail the cortical and subcortical anatomy of the central core of the brain, defining its limits, with particular attention to the topography and relationships of the thalamus, basal ganglia, and related white matter pathways and vessels.

METHODS The authors studied 19 cerebral hemispheres. The vascular systems of all of the specimens were injected with colored silicone, and the specimens were then frozen for at least 1 month to facilitate identification of individual fiber tracts. The dissections were performed in a stepwise manner, locating each gray matter nucleus and white matter pathway at different depths inside the central core. The course of fiber pathways was also noted in relation to the insular limiting sulci.

RESULTS The insular surface is the most superficial aspect of the central core and is divided by a central sulcus into an anterior portion, usually containing 3 short gyri, and a posterior portion, with 2 long gyri. It is bounded by the anterior limiting sulcus, the superior limiting sulcus, and the inferior limiting sulcus. The extreme capsule is directly underneath the insular surface and is composed of short association fibers that extend toward all the opercula. The claustrum lies deep to the extreme capsule, and the external capsule is found medial to it. Three fiber pathways contribute to form both the extreme and external capsules, and they lie in a sequential anteroposterior disposition: the uncinate fascicle, the inferior fronto-occipital fascicle, and claustrocortical fibers. The putamen and the globus pallidus are between the external capsule, laterally, and the internal capsule, medially. The internal capsule is present medial to almost all insular limiting sulci and most of the insular surface, but not to their most anteroinferior portions. This anteroinferior portion of the central core has a more complex anatomy and is distinguished in this paper as the “anterior perforated substance region.” The caudate nucleus and thalamus lie medial to the internal capsule, as the most medial structures of the central core. While the anterior half of the central core is related to the head of the caudate nucleus, the posterior half is related to the thalamus, and hence to each associated portion of the internal capsule between these structures and the insular surface. The central core stands on top of the brainstem. The brainstem and central core are connected by several white matter pathways and are not separated from each other by any natural division. The authors propose a subdivision of the central core into quadrants and describe each in detail. The functional importance of each structure is highlighted, and surgical approaches are suggested for each quadrant of the central core.

CONCLUSIONS As a general rule, the internal capsule and its vascularization should be seen as a parasagittal barrier with great functional importance. This is of particular importance in choosing surgical approaches within this region.

Quantitative anatomical analysis and clinical experience with mini-pterional and mini-orbitozygomatic approaches for intracranial aneurysm surgery

J Neurosurg 127:646–659, 2017

The aim of this investigation was to modify the mini-pterional and mini-orbitozygomatic (mini-OZ) approaches in order to reduce the amount of tissue traumatization caused and to compare the use of the 2 approaches in the removal of circle of Willis aneurysms based on the authors’ clinical experience and quantitative analysis.

METHODS Three formalin-fixed adult cadaveric heads injected with colored silicone were examined. Surgical freedom and angle of attack of the mini-pterional and mini-OZ approaches were measured at 9 anatomical points, and the measurements were compared. The authors also retrospectively reviewed the cases of 396 patients with ruptured and unruptured single aneurysms in the circle of Willis treated by microsurgical techniques at their institution between January 2006 and November 2014.

RESULTS A significant difference in surgical freedom was found in favor of the mini-pterional approach for access to the ipsilateral internal carotid artery (ICA) and middle cerebral artery (MCA) bifurcations, the most distal point of the ipsilateral posterior cerebral artery (PCA), and the basilar artery (BA) tip. No statistically significant differences were found between the mini-pterional and mini-OZ approaches for access to the posterior clinoid process, the most distal point of the superior cerebellar artery (SCA), the anterior communicating artery (ACoA), the contralateral ICA bifurcation, and the most distal point of the contralateral MCA. A trend toward increasing surgical freedom was found for the mini-OZ approach to the ACoA and the contralateral ICA bifurcation. The lengths exposed through the mini-OZ approach were longer than those exposed by the mini-pterional approach for the ipsilateral PCA segment (11.5 ± 1.9 mm) between the BA and the most distal point of the P2 segment of the PCA, for the ipsilateral SCA (10.5 ± 1.1 mm) between the BA and the most distal point of the SCA, and for the contralateral anterior cerebral artery (ACA) (21 ± 6.1 mm) between the ICA bifurcation and the most distal point of the A2 segment of the ACA. The exposed length of the contralateral MCA (24.2 ± 8.6 mm) between the contralateral ICA bifurcation and the most distal point of the MCA segment was longer through the mini-pterional approach. The vertical angle of attack (anteroposterior direction) was significantly greater with the minipterional approach than with the mini-OZ approach, except in the ACoA and contralateral ICA bifurcation. The horizontal angle of attack (mediolateral direction) was similar with both approaches, except in the ACoA, contralateral ICA bifurcation, and contralateral MCA bifurcation, where the angle was significantly increased in the mini-OZ approach.

CONCLUSIONS The mini-pterional and mini-OZ approaches, as currently performed in select patients, provide less tissue traumatization (i.e., less temporal muscle manipulation, less brain parenchyma retraction) from the skin to the aneurysm than standard approaches. Anatomical quantitative analysis showed that the mini-OZ approach provides better exposure to the contralateral side for controlling the contralateral parent arteries and multiple aneurysms. The mini-pterional approach has greater surgical freedom (maneuverability) for ipsilateral circle of Willis aneurysms.


Is less always better? Keyhole and standard subtemporal approaches

J Neurosurg 127:157–164, 2017

The subtemporal approach is one of the surgical routes used to reach the interpeduncular fossa. Keyhole subtemporal approaches and zygomatic arch osteotomy have been proposed in an effort to decrease the amount of temporal lobe retraction. However, the effects of these modified subtemporal approaches on temporal lobe retraction have never been objectively validated.

METHODS A keyhole and a classic subtemporal craniotomy were executed in 4 fresh-frozen silicone-injected cadaver heads. The target was defined as the area bordered by the superior cerebellar artery, the anterior clinoid process, supraclinoid internal carotid artery, and the posterior cerebral artery. Once the target was fully visualized, the authors evaluated the amount of temporal lobe retraction by measuring the distance between the base of the middle fossa and the temporal lobe. In addition, the volume of the surgical and anatomical corridors was assessed as well as the surgical maneuverability using navigation and 3D moldings. The same evaluation was conducted after a zygomatic osteotomy was added to the two approaches.

RESULTS Temporal lobe retraction was the same in the two approaches evaluated while the surgical corridor and the maneuverability were all greater in the classic subtemporal approach.

CONCLUSIONS The zygomatic arch osteotomy facilitates the maneuverability and the surgical volume in both approaches, but the temporal lobe retraction benefit is confined to the lateral part of the middle fossa skull base and does not result in the retraction necessary to expose the selected target.

The force pyramid: a spatial analysis of force application during virtual reality brain tumor resection

J Neurosurg 127:171–181, 2017

Virtual reality simulators allow development of novel methods to analyze neurosurgical performance. The concept of a force pyramid is introduced as a Tier 3 metric with the ability to provide visual and spatial analysis of 3D force application by any instrument used during simulated tumor resection. This study was designed to answer 3 questions: 1) Do study groups have distinct force pyramids? 2) Do handedness and ergonomics influence force pyramid structure? 3) Are force pyramids dependent on the visual and haptic characteristics of simulated tumors?

METHODS Using a virtual reality simulator, NeuroVR (formerly NeuroTouch), ultrasonic aspirator force application was continually assessed during resection of simulated brain tumors by neurosurgeons, residents, and medical students. The participants performed simulated resections of 18 simulated brain tumors with different visual and haptic characteristics. The raw data, namely, coordinates of the instrument tip as well as contact force values, were collected by the simulator. To provide a visual and qualitative spatial analysis of forces, the authors created a graph, called a force pyramid, representing force sum along the z-coordinate for different xy coordinates of the tool tip.

RESULTS Sixteen neurosurgeons, 15 residents, and 84 medical students participated in the study. Neurosurgeon, resident and medical student groups displayed easily distinguishable 3D “force pyramid fingerprints.” Neurosurgeons had the lowest force pyramids, indicating application of the lowest forces, followed by resident and medical student groups. Handedness, ergonomics, and visual and haptic tumor characteristics resulted in distinct well-defined 3D force pyramid patterns.

CONCLUSIONS Force pyramid fingerprints provide 3D spatial assessment displays of instrument force application during simulated tumor resection. Neurosurgeon force utilization and ergonomic data form a basis for understanding and modulating resident force application and improving patient safety during tumor resection.


Novel method for dynamic control of intracranial pressure

J Neurosurg 126:1629–1640, 2017

Intracranial pressure (ICP) pulsations are generally considered a passive result of the pulsatility of blood flow. Active experimental modification of ICP pulsations would allow investigation of potential active effects on blood and CSF flow and potentially create a new platform for the treatment of acute and chronic low blood flow states as well as a method of CSF substance clearance and delivery. This study presents a novel method and device for altering the ICP waveform via cardiac-gated volume changes.

METHODS The novel device used in this experiment (named Cadence) consists of a small air-filled inelastic balloon (approximately 1.0 ml) implanted into the intracranial space and connected to an external programmable pump, triggered by an R-wave detector. Balloons were implanted into the epidural space above 1 of the hemispheres of 19 canines for up to 10 hours. When activated, the balloons were programed to cyclically inflate with the cardiac cycle with variable delay, phase, and volume. The ICP response was measured in both hemispheres. Additionally, cerebral blood flow (heat diffusion and laser Doppler) was studied in 16 canines.

RESULTS This system, depending on the inflation pattern of the balloon, allowed a flattening of the ICP waveform, increase in the ICP waveform amplitude, or phase shift of the wave. This occurred with small mean ICP changes, typically around ± 2 mm Hg (15%). Bilateral ICP effects were observed with activation of the device: balloon inflation at each systole increased the systolic ICP pulse (up to 16 mm Hg, 1200%) and deflation at systole decreased or even inverted the systolic ICP pulse (-0.5 to -19 mm Hg, -5% to -1600%) in a dose-(balloon volume) dependent fashion. No aphysiological or deleterious effects on systemic pressure (≤ ±10 mm Hg; 13% change in mean pressure) or cardiac rate (≤ ± 17 beats per minute; 16% change) were observed during up to 4 hours of balloon activity.

CONCLUSIONS The results of these initial studies using an intracranially implanted, cardiac-gated, volume-oscillating balloon suggest the Cadence device can be used to modify ICP pulsations, without physiologically deleterious effects on mean ICP, systemic vascular effects, or brain injury. This device and technique may be used to study the role of ICP pulsatility in intracranial hemo- and hydrodynamic processes and introduces the creation of a potential platform of a cardiac-gated system for treatment of acute and chronic low blood flow states, and diseases requiring augmentation of CSF substance clearance or delivery.

Transtentorial transcollateral sulcus approach to the ventricular atrium

J Neurosurg 126:1246–1252, 2017

Conventional approaches to the atrium of the lateral ventricle may be associated with complications related to direct cortical injury or brain retraction. The authors describe a novel approach to the atrium through a retrosigmoid transtentorial transcollateral sulcus corridor.

METHODS: Bilateral retrosigmoid craniotomies were performed on 4 formalin-fixed, colored latex–injected human cadaver heads (a total of 8 approaches). Microsurgical dissections were performed under 3× to 24× magnification, and endoscopic visualization was provided by 0° and 30° rigid endoscope lens systems. Image guidance was provided by coupling an electromagnetic tracking system with an open source software platform. Objective measurements on cortical thickness traversed and total depth of exposure were recorded. Additionally, the basal occipitotemporal surfaces of 10 separate cerebral hemisphere specimens were examined to define the surface topography of sulci and gyri, with attention to the appearance and anatomical patterns and variations of the collateral sulcus and the surrounding gyri.

RESULTS: The retrosigmoid approach allowed for clear visualization of the basal occipitotemporal surface. The collateral sulcus was identified and permitted easy endoscopic access to the ventricular atrium. The conical corridor thus obtained provided an average base working area of 3.9 cm2 at an average depth of 4.5 cm. The mean cortical thickness traversed to enter the ventricle was 1.4 cm. The intraventricular anatomy of the ipsilateral ventricle was defined clearly in all 8 exposures in this manner. The anatomy of the basal occipitotemporal surface, observed in a total of 18 hemispheres, showed a consistent pattern, with the collateral sulcus abutted by the parahippocampal gyrus medially, and the fusiform and lingual gyrus laterally. The collateral sulcus was found to be caudally bifurcated in 14 of the 18 specimens.

CONCLUSIONS: The retrosigmoid supracerebellar transtentorial transcollateral sulcus approach is technically feasible. This approach has the potential advantage of providing a short and direct path to the atrium, hence avoiding violation of deep neurovascular structures and preserving eloquent areas. Although this approach appears unconventional, it may provide a minimally invasive option for the surgical management of selected lesions within the atrium of the lateral ventricle.


Occipitocervical Instability After Far-Lateral Transcondylar Surgery

Neurosurgery 80:140–145, 2017

After a far-lateral transcondylar approach, patients may maintain neutral alignment in the immediate postoperative period, but severe occipitoatlantal subluxation may occur gradually with cranial settling and possible neurological injury. Previous research is based on assumptions regarding the extent of condylar resection and the change in biomechanics that produces instability.

OBJECTIVE: To quantify the extent of bone removal during a far-lateral transcondylar approach, determine the changes in range of motion (ROM) and stiffness that occur after condylar resection, and identify the threshold of condylar resection that predicts alterations in occipitocervical biomechanics.

METHODS: Nine human cadaveric specimens were biomechanically tested before and after far-lateral transcondylar resection extending into the hypoglossal canal (HC). The extent of condylar resection was quantified using volumetric comparison between pre- and postresection computed tomography scans. ROM and stiffness testing were performed in intact and resected states. The extent of resection that produced alterations in occipitocervical biomechanics was assessed with sensitivity analysis.

RESULTS: Bone removal during condylar resection into the HC was 15.4%-63.7% (mean 35.7%). Sensitivity analysis demonstrated that changes in biomechanics may occur when just 29% of the occipital condyle was resected (area under the curve 0.80-1.00).

CONCLUSION: Changes in occipitocervical biomechanics may be observed if one-third of the occipital condyle is resected. During surgery, the HC may not be a reliable landmark to guide the extent of resection. Patients who undergo condylar resections extending into or beyond the HC require close surveillance for occipitocervical instability.

A prospective randomized multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART disk plus autologous disk chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disks to avoid secondary disease

Neurosurg Rev (2017) 40:155–162

NOVOCART ® Disk plus, an autologous cell compound for autologous disk chondrocyte transplantation, was developed to reduce the degenerative sequel after lumbar disk surgery or to prophylactically avoid degeneration in adjacent disks, if present. The NDisc trial is an on-going multi-center, randomized study with a sequential phase I study within the combined phase I/II trial with close monitoring of tolerability and safety.

Twenty-four adult patients were randomized and treated with the investigational medicinal product NDisc plus or the carrier material only. Rates of adverse events in Phase I of this trial were comparable with those expected in the early time course after elective disk surgery. There was one reherniation 7 months after transplantation, which corresponds to an expected reherniation rate. Immunological markers like CRP and IL-6 were not significantly elevated and there were no im- aging abnormalities. No indications of harmful material extrusion or immunological consequences due to the investigational medicinal product NDplus were observed.

Therefore, the study appears to be safe and feasible. Safety analyses of Phase I of this trial indicate a relatively low risk considering the benefits that patients with debilitating degenerative disk disease may gain.


Virtual and stereoscopic anatomy: when virtual reality meets medical education


J Neurosurg 125:1105–1111, 2016

The authors sought to construct, implement, and evaluate an interactive and stereoscopic resource for teaching neuroanatomy, accessible from personal computers.

Methods Forty fresh brains (80 hemispheres) were dissected. Images of areas of interest were captured using a manual turntable and processed and stored in a 5337-image database. Pedagogic evaluation was performed in 84 graduate medical students, divided into 3 groups: 1 (conventional method), 2 (interactive nonstereoscopic), and 3 (interactive and stereoscopic). The method was evaluated through a written theory test and a lab practicum.

Results Groups 2 and 3 showed the highest mean scores in pedagogic evaluations and differed significantly from Group 1 (p < 0.05). Group 2 did not differ statistically from Group 3 (p > 0.05). Size effects, measured as differences in scores before and after lectures, indicate the effectiveness of the method. ANOVA results showed significant difference (p < 0.05) between groups, and the Tukey test showed statistical differences between Group 1 and the other 2 groups (p < 0.05). No statistical differences between Groups 2 and 3 were found in the practicum. However, there were significant differences when Groups 2 and 3 were compared with Group 1 (p < 0.05).

Conclusions The authors conclude that this method promoted further improvement in knowledge for students and fostered significantly higher learning when compared with traditional teaching resources.

Pulsatile Dynamics of the Optic Nerve Sheath and Intracranial Pressure


Neurosurgery 79:100–107, 2016

Raised intracranial pressure (ICP) may lead to increased stiffness of the optic nerve sheath (ONS).

OBJECTIVE: To develop a method for analyzing ONS dynamics from transorbital ultrasound and investigate a potential difference between patients with raised ICP vs normal ICP.

METHODS: We retrospectively analyzed data from 16 patients (#12 years old) for whom ultrasound image sequences of the ONS had been acquired from both eyes just before invasive measurement of ICP. Eight patients had an ICP $20 mm Hg. The transverse motion on each side of the ONS was estimated from ultrasound, and Fourier analysis was used to extract the magnitude of the displacement corresponding to the heart rate. By calculating the normalized absolute difference between the displacements on each side of the ONS, a measure of ONS deformation was obtained. This parameter was referred to as the deformability index. According to our hypothesis, because deformability is inversely related to stiffness, we expected this parameter to be lower for ICP $20 mm Hg compared with ICP ,20 mm Hg. The one-sided Mann-Whitney U test was used for statistical comparison.

RESULTS: The deformability index was significantly lower in the group with ICP $20 mm Hg (median value 0.11 vs 0.24; P = .002).

CONCLUSION: We present a method for assessment of ONS pulsatile dynamics using transorbital ultrasound imaging. A significant difference was noted between the patient groups, indicating that deformability of the ONS may be relevant as a noninvasive marker of raised ICP. The clinical implications are promising and should be investigated in future clinical studies.

The nondecussating pathway of the dentatorubrothalamic tract in humans

The nondecussating pathway of the dentatorubrothalamic tract in humans

J Neurosurg 124:1406–1412, 2016

The dentatorubrothalamic tract (DRTT) is the major efferent cerebellar pathway arising from the dentate nucleus (DN) and decussating to the contralateral red nucleus (RN) and thalamus. Surprisingly, hemispheric cerebellar output influences bilateral limb movements. In animals, uncrossed projections from the DN to the ipsilateral RN and thalamus may explain this phenomenon. The aim of this study was to clarify the anatomy of the dentatorubrothalamic connections in humans.

Methods The authors applied advanced deterministic fiber tractography to a template of 488 subjects from the Human Connectome Project (Q1–Q3 release, WU-Minn HCP consortium) and validated the results with microsurgical dissection of cadaveric brains prepared according to Klingler’s method.

Results The authors identified the “classic” decussating DRTT and a corresponding nondecussating path (the nondecussating DRTT, nd-DRTT). Within each of these 2 tracts some fibers stop at the level of the RN, forming the dentatorubro tract and the nondecussating dentatorubro tract. The left nd-DRTT encompasses 21.7% of the tracts and 24.9% of the volume of the left superior cerebellar peduncle, and the right nd-DRTT encompasses 20.2% of the tracts and 28.4% of the volume of the right superior cerebellar peduncle.

Conclusions The connections of the DN with the RN and thalamus are bilateral, not ipsilateral only. This affords a potential anatomical substrate for bilateral limb motor effects originating in a single cerebellar hemisphere under physiological conditions, and for bilateral limb motor impairment in hemispheric cerebellar lesions such as ischemic stroke and hemorrhage, and after resection of hemispheric tumors and arteriovenous malformations. Furthermore, when a lesion is located on the course of the dentatorubrothalamic system, a careful preoperative tractographic analysis of the relationship of the DRTT, nd-DRTT, and the lesion should be performed in order to tailor the surgical approach properly and spare all bundles.

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